Endothelium-derived vasoactive substances
In 1980, Furchgott and Zawadski established the role of vascular endothelium in mediating the relaxation of arterial smooth muscle to acetylcholine (Furchgott & Zawadski, 1980). Many other substances, whose ability to initiate changes in vascular tone also depends on the integrity of the endothelium, were soon discovered. These substances include vasopressin (Katusic, Shepherd & Vanhoutte, 1984), bradykinin (Cherry et al., 1982), angiotensin II (Toda, 1984), ADP (De Mey & Vanhoutte, 1981), ATP (Burnstock & Kennedy, 1985), noradrenaline and serotonin (Cocks & Angus, 1983). In order to produce their effect, these substances bind to specific receptors located on the surface of endothelial cells and subsequently provoke the release of an endothelial factor which acts on the vascular smooth muscle cells. This diffusible factor, termed endothelium-derived relaxing factor (EDRF), with a very short biological half-life, was identified in 1987 as nitric oxide (Ignarro et al., 1987; Khan & Furchgott, 1987; Palmer, Ferrige & Moncada, 1987) or a related labile nitroso compound (Rubanyi et al., 1989). However, it has been recognised that not all endothelium-dependent vascular responses can be explained by release of nitric oxide (Rubanyi & Vanhoutte, 1987). Prostacyclin is also released by endothelial cells and mediates vasodilation (Moncada et al., 1976). The existence of a substance mediating endothelium-dependent hyperpolarisation of smooth muscle has also been postulated (Komori & Suzuki, 1987). Soon after the discovery of EDRF, it was shown that endothelial cells could mediate vasoconstriction as well as vasodilatation (De Mey & Vanhoutte, 1982).